miR-542-3p Contributes to the HK2-Mediated High Glycolytic Phenotype in Human Glioma Cells

Abstract

(1) Background: The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear; (2) Methods: We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis; (3) Results: We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database; (4) Conclusions: miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells.

Systematic characterization and biological functions of non‐coding RNAs in glioblastoma

“…High expression of miR‐1258 , miR‐935 and miR‐128‐3p was associated with better overall survival (OS) in patients with GBM, 23 , 24 , 25 while low miR‐542‐3p and miR‐221/222 clusters expression was associated with better OS in patients with GBM. 26 , 27 Previous studies evaluated the effect of cell‐free circulating RNA on patients with GBM. Nadaradjane et al 28 found that miR‐370‐3p could be treated in patients with GBM by enhancing temozolomide sensitivity, while it could not be used as a cell‐free circulating biomarker and was not associated with patient OS.…”

“… 19 , 34 , 35 Previous studies have found that miR‐27a‐3p can also enhance the resistance of patients with GBM to temozolomide, which is closely associated with poor OS. 34 In addition, Kim et al 27 found that miR‐542‐3p could induce the glycolytic activity of GBM cells by activating hexokinase 2, thus promoting cell proliferation and chemotherapy resistance, leading to reduced OS in patients.…”

“…The average survival time of patients with glioma is 12–15 months, the 5‐year survival rate is <5%, and the survival and prognosis of patients with GBM are worse 22 ; thus, it is important to evaluate the patient's prognosis. High expression of miR‐1258 , miR‐935 and miR‐128‐3p was associated with better overall survival (OS) in patients with GBM, 23–25 while low miR‐542‐3p and miR‐221/222 clusters expression was associated with better OS in patients with GBM 26,27 . Previous studies evaluated the effect of cell‐free circulating RNA on patients with GBM.…”

Interplay Among Metabolism, Epigenetic Modifications, and Gene Expression in Cancer

“…MiR-9-1 targets HK2 to inhibit glycolysis, reduce the formation of lactic acid, and promote metabolic reprogramming in nasopharyngeal carcinoma cells (Xu Q. L. et al, 2021). Meanwhile, miR-542-3p elevates HK2 to induce glycolysis in GBM (Kim et al, 2021). miRNA-1185-2-3p inhibits Golgi phosphoprotein 3 (GOLPH3L) and affects central carbon metabolism regulated by GOLPH3L (Xu et al, 2021b).…”

MicroRNA-542 suppressed the proliferation of human glioma cells by targeting talin-2 (TLN2)

“…MiR-542 acts as a tumor-suppressor in human malignancies e.g., liver cancer, by regulating the expression of specific molecular targets [9]. There are limited reports on the regulatory role of miR-542 in human glioma [10]. The present study was carried out to investigate the role of miR-542 in glioma cells.…”